The central theme of this Program is based on the axiom that, during early stages of development, organisms are uniquely vulnerable to environmental challenges that constrain the physiological and behavioral phenotypes that are manifest throughout the rest of the life span of the organism. Understanding the mechanisms that confer risk or resistance to these challenges is the fundamental goal of the work done in all of the projects. The first Project, "Activity and Responses to Hypoxia/Nicotine in Development" examines the risks conferred on the developing fetal baboon by nicotine in smoking cessation programs for pregnant women and in understanding postnatal vulnerabilities of these infants for SIDS, attention deficits, and other neurobehavioral disorders. The second project, "Activity and Responses to Nutrient and Oxygen Supply" focuses on nutritional challenges experienced by the growth restricted fetal lambs and by very low birth weight infants during their adjustment to extra- uterine life. Knowledge of the short-term physiological responses and adaptations to variation in nutrient supply are the logical starting point for understand the long-term risks associated with inadequate nutrition early in life. The third project, "Perinatal Nutrition and Mechanisms of Adult Disease", addresses the long-term consequences of nutrient deprivation early in life. Research focuses on changes in placental and fetal gene expression that represent proximal steps associated with nutrient programming, the role of endogenous versus exogenous factors in stabilizing the programmed phenotype and how later nutrition and growth serve to amplify effects of fetal programming. An administrative, statistical and computer Core and molecular/bioanalytical Core support the needs of the research.